线粒体磷酸烯醇丙酮酸羧激酶 (PCK2) 通过调节 AMPK/ULK1 依赖性自噬来调节成骨分化,STEM CELLS

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线粒体磷酸烯醇丙酮酸羧激酶 (PCK2) 通过调节 AMPK/ULK1 依赖性自噬来调节成骨分化
STEM CELLS ( IF 4.0 ) Pub Date : 2019-10-14 , DOI: 10.1002/stem.3091
Zheng Li _{1,

2} , Xuenan Liu _{1,

2} , Yuan Zhu _{1,

2} , Yangge Du _{1,

2} , Xuejiao Liu _{1,

2} , Longwei Lv _{1,

2} , Xiao Zhang _{1,

2} , Yunsong Liu _{1,

2} , Ping Zhang _{1,

2} , Yongsheng Zhou _{1,

2}

Affiliation

线粒体磷酸烯醇丙酮酸羧激酶 (PCK2) 是一种限速酶，在多种生理过程中起着关键作用。PCK2 的失代偿导致各种能量代谢紊乱。然而，关于 PCK2 对人类间充质干细胞 (hMSCs) 成骨的影响知之甚少。在这里，我们报告了 PCK2 作为 MSCs 成骨分化的正调节剂的新功能。除了众所周知的合成代谢作用外，我们还证明 PCK2 调节自噬。PCK2 缺乏显着抑制自噬，导致 MSCs 的成骨能力受损。另一方面，PCK2 过表达促进了自噬；这伴随着MSCs的成骨分化增加。而且，PCK2 通过 AMP 活化蛋白激酶 (AMPK)/unc-51 像自噬激活激酶 1(ULK1) 依赖的自噬调节 MSC 的成骨分化。总的来说，我们目前的研究揭示了 PCK2 在整合自噬和骨形成方面的新作用，为基于干细胞的骨组织工程提供了一个潜在的靶点，可能会改善代谢性骨病的治疗方法。干细胞 2019；37：1542–1555

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Mitochondrial phosphoenolpyruvate carboxykinase (PCK2) regulates osteogenic differentiation by modulating AMPK/ULK1-dependent autophagy

Mitochondrial phosphoenolpyruvate carboxykinase (PCK2) is a rate‐limiting enzyme that plays critical roles in multiple physiological processes. The decompensation of PCK2 leads to various energy metabolic disorders. However, little is known regarding the effects of PCK2 on osteogenesis by human mesenchymal stem cells (hMSCs). Here, we report a novel function of PCK2 as a positive regulator of MSCs osteogenic differentiation. In addition to its well‐known role in anabolism, we demonstrate that PCK2 regulates autophagy. PCK2 deficiency significantly suppressed autophagy, leading to the impairment of osteogenic capacity of MSCs. On the other hand, autophagy was promoted by PCK2 overexpression; this was accompanied by increased osteogenic differentiation of MSCs. Moreover, PCK2 regulated osteogenic differentiation of MSCs via AMP‐activated protein kinase (AMPK)/unc‐51 like autophagy activating kinase 1(ULK1)‐dependent autophagy. Collectively, our present study unveiled a novel role for PCK2 in integrating autophagy and bone formation, providing a potential target for stem cell‐based bone tissue engineering that may lead to improved therapies for metabolic bone diseases. Stem Cells 2019;37:1542–1555

更新日期：2019-10-14

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